Bone Drug Might Help in Schizophrenia

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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

A drug (raloxifene (Keoxifene) aimed at preventing osteoporosis appears to help the cognitive deficits associated with schizophrenia.

Note that adverse events associated with raloxifene were similar to those seen in the placebo group.

TORONTO -- A drug aimed at preventing osteoporosis appears to help the cognitive deficits associated with schizophrenia, a researcher said here.

In a randomized trial, daily raloxifene (Keoxifene) improved working memory and attention/processing speed, according to Tom Weickert, PhD, of the University of New South Wales in Kensington, Australia.

There's substantial evidence that estrogen has benefits in preserving memory and attention, Weickert and colleagues noted, and studies have showed that in healthy aging men and in postmenopausal women, raloxifene preserved brain activity during a memory challenge.

To test the effect in schizophrenia, they recruited patients for a randomized, placebo-controlled crossover study at two sites in Australia. They excluded patients who had comorbid psychopathology, a recent history of drug abuse, or head trauma, as well as several other factors that might have led to cognitive difficulties.

All told, 93 patients ages 18 through 51, were randomly assigned to placebo or 120 milligrams daily of raloxifene for 6 weeks. The initial phase was followed by a 1-week washout period and patients then transferred to the opposite treatment for another 6 weeks. Some 79 patients were available for the final analysis.

The researchers tested cognition at baseline and at the end of each 60-seek treatment period, Weickert said, using standard tests for working memory, verbal fluency, attention/perceptual-motor processing speed, and verbal memory.

They assessed symptom severity at the same times using the Positive and Negative Syndrome Scale (PANSS), as well as measuring depression, general health, and quality of life.

The investigators also collected blood to assess the effect of raloxifene on such things as prothrombin time and antithrombin III deficiency, Weickert reported.

Analysis suggested there were significant carryover effects that blunted any difference between placebo and raloxifene during the second 6-week treatment period, Weickert said.

For that reason, the researchers presented the results from the first 6 weeks as a parallel group analysis, he said.

In that analysis, they found:

Of the 40 patients who got raloxifene, 16 showed "clinically reliable change" on one or more of the cognitive measures, versus six out of 39 patients getting placebo.

Overall, raloxifene patients were significantly more likely to improve on the Wechsler Memory Scale Revised Logical Memory I and II, as well as on the Trail Making Test A.

There was no effect on symptom scores using the PANSS, or on depression, general health, or quality of life.

There were statistically significant effects of raloxifene on the blood measures, but no clinically relevant changes on the hormone and coagulation panel measures.

Aside from that, adverse events associated with raloxifene were similar to those seen in the placebo group.

"The results show for the first time," Weickert said, "that an adjunctive raloxifene treatment ... can improve verbal memory, implicit learning, attention, and processing speed."

"These findings support the hypothesis of the estrogen-related disease model for schizophrenia and can provide a potential novel treatment in both men and women," he added.

The study puts a renewed and welcome spotlight on cognition in schizophrenia, commented Ma-Li Wong, MD, of Flinders University in Adelaide Australia, and an associate editor of the journal, who was not part of the study but who delivered a commentary during the session at which it was presented.

The diagnostic criteria for schizophrenia, she noted, say little about cognition "but any psychiatrist will tell you that ... problems with cognition are pervasive."

"Much more needs to be understood about cognitive impairments in schizophrenia," she said.

Until now, there has been little that physicians could do to help, she said, but the paper "brings hope that we may one day effectively address cognitive decline and understand more about its psychopathology" in schizophrenia patients.

In particular, she said, it was interesting that the declines seen in the study were independent of age and sex, suggesting that treatment might also be independent of those factors.

The study had support from the University of New South Wales. the National Health and Medical Research Council of Australia, Neuroscience Research Australia, the Schizophrenia Research Institute, the Macquarie Group Foundation, the Australian Schizophrenia Research Bank, the Pratt Foundation, Ramsay Health Care, and the Viertel Charitable Foundation. Weickert said he had no relevant disclosures.

Wong did not make any disclosures.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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